(12) MEIOC prevents continued mitotic cycling prior to meiotic entry during mouse oogenesis

Maria M. Mikedis^1;2;3; Esther Ushuhuda¹; Jenniluyn Nguyen³; Natalie Pfaltzgraff¹

1. Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States

2. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH United States

3. Whitehead Institute, Cambridge, MA, United States 


Abstract Text:

In multicellular organisms, germ cells’ transformation into haploid gametes requires that they transition from mitosis to meiosis, whereby they stop mitotic cycling and enter the meiotic cell cycle. In mammals, transcriptional activator STRA8-MEIOSIN mediates the decision to enter the meiotic cell cycle by triggering the G1-to-meiotic S phase transition. However, the molecular basis by which mammalian germ cells prevent continued mitotic cycling before entering the meiotic cell cycle remains unclear. Here, we investigate MEIOC’s role in the mitosis-to-meiosis transition during mouse oogenesis by analyzing proliferation, cell cycle transcriptomics, and cell cycle associated-protein expression. MEIOC was previously shown to destabilize mRNA and repress the mitotic program after meiotic entry. Here, we demonstrate that MEIOC prevents continued mitotic cycling prior to meiotic entry in oogenic cells. We find that the mitosis-to-meiosis transition involves the repression of G1/S cyclin CCNA2 at the transcript and protein levels, and that MEIOC downregulates CCNA2 protein expression, likely by destabilizing its mRNA. In addition, MEIOC promotes entry into meiotic S phase by indirectly increasing Meiosin transcript abundance and consequently activating the STRA8-MEIOSIN transcription factor. We conclude that, in mouse oogenic cells, the transition from mitosis to meiosis occurs as two molecularly regulated steps– (i) halt of mitotic cycling and (ii) entry into the meiotic cell cycle – and that MEIOC rewires the cell cycle program to facilitate both steps in this transition.